Study of NGR-hTNF in Combination With Doxorubicin in Patients Affected by Advanced or Metastatic Ovarian Cancer
Primary Purpose
Ovarian Cancer Metastatic Recurrent
Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
NGR-hTNF
doxorubicin
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Cancer Metastatic Recurrent focused on measuring NGR-hTNF, Ovarian cancer, Doxorubicin
Eligibility Criteria
Inclusion Criteria:
- Patients ≥18 years old affected by advanced or metastatic ovarian cancer previously treated with platinum regimens (cis or carboplatin) plus paclitaxel and with documented progression disease within 6 months from last chemotherapy administered (refractory/resistant population) or in progression disease after 6 months from last chemotherapy (platinum regimens plus paclitaxel) administered
- Rechallenge with platinum regimens
- No previous exposure to anthracyclines
- Histologically or cytologically confirmed ovarian carcinoma
- Life expectancy more than 3 months
- ECOG Performance status 0 - 1
- Normal cardiac function (LVEF ≥55%) and absence of uncontrolled hypertension
- Measurable disease defined as ≥1 unidimensional measurable lesion ≥ 20 mm by conventional technics or ≥ 10 mm ( spiral CT scan or PET); ascites is allowed if present with peritoneal carcinosis
Adequate baseline bone marrow, hepatic and renal function, defined as follows:
- Neutrophils > 1.5 x 10^9/L and platelets > 100 x 10^9/L
- Bilirubin < 1.5 x ULN
- AST and/or ALT < 2.5 x ULN in absence of liver metastasis
- AST and/or ALT < 5 x ULN in presence of liver metastasis
- Serum creatinine < 1.5 x ULN
Patients may have had prior therapy providing the following conditions are met:
- Chemotherapy and radiotherapy: wash-out period of 28 days
- Surgery: wash-out period of 14 days
- Absence of any conditions in which hypervolaemia and its consequences (e.g. increased stroke volume, elevated blood pressure) or haemodilution could represent a risk for the patient (take as reference "Technical data sheet human albumin" specifically used in Pharmacy Department for NGR-hTNF dilution)
- Patients must give written informed consent to participate in the study
Exclusion criteria:
- Concurrent anticancer therapy
- Patients must not receive any other investigational agents while on study
- New York Heart Association class II-IV cardiac disease
- Acute angina
- Patients with myocardial infarction within the last six (6) months
- Patient with significant peripheral vascular disease
- Thrombosis of main portal vein
- Clinical signs of CNS involvement
- Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol
- Known hypersensitivity/allergic reaction to human albumin preparations or to any of the excipients
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol
- Pregnancy or lactation. Patients with reproductive potential (i.e. menopausal for less than 1-year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration.
Sites / Locations
- Fondazione San Raffaele del Monte Tabor
- Policlinico Universitario A. Gemelli
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
A: NGR-hTNF + doxorubicin
Arm Description
NGR-hTNF plus doxorubicin
Outcomes
Primary Outcome Measures
Antitumor activity defined as response rate
Evaluated according to Response evaluation criteria in solid tumors (RECIST)
Secondary Outcome Measures
Progression Free Survival (PFS)
PFS evaluated according to Response evaluation criteria in solid tumors (RECIST)
Overall survival (OS)
Defined as the time from the date of randomization until the date of death due to any cause or the last date the patient was known to be alive
CA125 (U/mL) measurement
Tumor marker evaluation
Safety according to NCI-CTCAE criteria (version 3)
To evaluate safety profile related to NGR-hTNF
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00484432
Brief Title
Study of NGR-hTNF in Combination With Doxorubicin in Patients Affected by Advanced or Metastatic Ovarian Cancer
Official Title
NGR012: A Phase II Study of NGR-hTNF Administered in Combination With Doxorubicin Every 3 Weeks in Patients Affected by Advanced or Metastatic Ovarian Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
November 2008 (Actual)
Primary Completion Date
June 2016 (Actual)
Study Completion Date
June 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AGC Biologics S.p.A.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The main objective of the trial is to document the response rate in patients affected by metastatic ovarian cancer, treated with NGR-hTNF plus doxorubicin. Safety will be established by clinical and laboratory assessment according to NCI-CTC criteria.
Detailed Description
This is a phase II, open-label,single arm, non-randomized study that will be conducted in patients affected by metastatic ovarian cancer, that will be conducted using Simon's two-stage design method.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer Metastatic Recurrent
Keywords
NGR-hTNF, Ovarian cancer, Doxorubicin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A: NGR-hTNF + doxorubicin
Arm Type
Experimental
Arm Description
NGR-hTNF plus doxorubicin
Intervention Type
Drug
Intervention Name(s)
NGR-hTNF
Intervention Description
NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every 3 week until confirmed evidence of disease progression or unacceptable toxicity occurs
Intervention Type
Drug
Intervention Name(s)
doxorubicin
Intervention Description
Doxorubicin: 60mg/m² every 3 weeks, until cumulative dose of 550 mg/m²
Primary Outcome Measure Information:
Title
Antitumor activity defined as response rate
Description
Evaluated according to Response evaluation criteria in solid tumors (RECIST)
Time Frame
during the study
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
PFS evaluated according to Response evaluation criteria in solid tumors (RECIST)
Time Frame
during the study
Title
Overall survival (OS)
Description
Defined as the time from the date of randomization until the date of death due to any cause or the last date the patient was known to be alive
Time Frame
from the date of randomization to the date of death, assessed up to 6 months
Title
CA125 (U/mL) measurement
Description
Tumor marker evaluation
Time Frame
from the randomization, every 6 weeks until the end of treatment
Title
Safety according to NCI-CTCAE criteria (version 3)
Description
To evaluate safety profile related to NGR-hTNF
Time Frame
during the study
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients ≥18 years old affected by advanced or metastatic ovarian cancer previously treated with platinum regimens (cis or carboplatin) plus paclitaxel and with documented progression disease within 6 months from last chemotherapy administered (refractory/resistant population) or in progression disease after 6 months from last chemotherapy (platinum regimens plus paclitaxel) administered
Rechallenge with platinum regimens
No previous exposure to anthracyclines
Histologically or cytologically confirmed ovarian carcinoma
Life expectancy more than 3 months
ECOG Performance status 0 - 1
Normal cardiac function (LVEF ≥55%) and absence of uncontrolled hypertension
Measurable disease defined as ≥1 unidimensional measurable lesion ≥ 20 mm by conventional technics or ≥ 10 mm ( spiral CT scan or PET); ascites is allowed if present with peritoneal carcinosis
Adequate baseline bone marrow, hepatic and renal function, defined as follows:
Neutrophils > 1.5 x 10^9/L and platelets > 100 x 10^9/L
Bilirubin < 1.5 x ULN
AST and/or ALT < 2.5 x ULN in absence of liver metastasis
AST and/or ALT < 5 x ULN in presence of liver metastasis
Serum creatinine < 1.5 x ULN
Patients may have had prior therapy providing the following conditions are met:
Chemotherapy and radiotherapy: wash-out period of 28 days
Surgery: wash-out period of 14 days
Absence of any conditions in which hypervolaemia and its consequences (e.g. increased stroke volume, elevated blood pressure) or haemodilution could represent a risk for the patient (take as reference "Technical data sheet human albumin" specifically used in Pharmacy Department for NGR-hTNF dilution)
Patients must give written informed consent to participate in the study
Exclusion criteria:
Concurrent anticancer therapy
Patients must not receive any other investigational agents while on study
New York Heart Association class II-IV cardiac disease
Acute angina
Patients with myocardial infarction within the last six (6) months
Patient with significant peripheral vascular disease
Thrombosis of main portal vein
Clinical signs of CNS involvement
Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol
Known hypersensitivity/allergic reaction to human albumin preparations or to any of the excipients
Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol
Pregnancy or lactation. Patients with reproductive potential (i.e. menopausal for less than 1-year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonio Lambiase, MD
Organizational Affiliation
AGC Biologics S.p.A.
Official's Role
Study Director
Facility Information:
Facility Name
Fondazione San Raffaele del Monte Tabor
City
Milan
Country
Italy
Facility Name
Policlinico Universitario A. Gemelli
City
Rome
ZIP/Postal Code
00168
Country
Italy
12. IPD Sharing Statement
Citations:
PubMed Identifier
22644293
Citation
Lorusso D, Scambia G, Amadio G, di Legge A, Pietragalla A, De Vincenzo R, Masciullo V, Di Stefano M, Mangili G, Citterio G, Mantori M, Lambiase A, Bordignon C. Phase II study of NGR-hTNF in combination with doxorubicin in relapsed ovarian cancer patients. Br J Cancer. 2012 Jun 26;107(1):37-42. doi: 10.1038/bjc.2012.233. Epub 2012 May 29.
Results Reference
result
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Study of NGR-hTNF in Combination With Doxorubicin in Patients Affected by Advanced or Metastatic Ovarian Cancer
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